One of the most unique aspects of the maternal-fetal relationship is the temporary tolerance of the female immune system to the developing embryo. Our preliminary investigations have shown that antigen specific T-cell suppressor factors (TsF) may play an important role in maintaining the immune tolerance observed between mother and fetus. A study of this phenomenon may provide understanding of many types of infertility, as well as provide insight into antigen specific immune suppression. Female mice were treated with a monoclonal antibody to TsF. Only 14% of the treated animals had viable pregnancies at Day 17. IN control animals, viable pregnancies were documented in 83% of the mated females. Also demonstrated was the presence of TsF in the placenta, fetus and uterus of pregnant females, while the uterus of nonpregnant females contained no detectable TsF. Other female tissues and male tissues contained no detectable TsF by Western blotting techniques, except for the spleen which contained measurable quantities of TsF. The present proposal outlines four specific aims to examine the role of antigen specific TsF during pregnancy. These are: (1) study the dynamics of the antipregnancy effects of monoclonal antibodies to TsF in outbred and inbred strains of mice bearing syngeneic and allogeneic fetuses. The minimal effective dosage, duration of action, and optimal time of administration will be studied. (2) Identify the tissues and cell types that produce the TsF which protects the fetus from the maternal immune system. (3) Characterize the biological specificity and activity of TsF and of the monoclonal antibodies to TsF on the maternal cellular and humoral immune responses. (4) Isolate and characterize TsF from the pregnant uterine tissue. These aims will help us determine the dynamics of T cell suppression of the maternal immune response to the fetus and the mechanism of the induction of suppressor factors. The data generated through this investigation will increase understanding of the regulation of the immune response during pregnancy and its contribution to pregnancy failure.